An examination of genetic data from the UK Biobank reveals that individuals with a higher genetically estimated lean body mass (i.e., the mass of muscles, bones, and non-fat tissues) exhibit a lower likelihood of developing Alzheimer’s disease. Additionally, those with a higher estimated lean mass in their arms and legs tended to demonstrate superior cognitive performance. The study was published in BMJ Medicine.
Alzheimer’s disease, a progressive neurodegenerative ailment, ranks as the predominant cause of dementia in older adults. This disorder stems from the accumulation of specific proteins in the brain, leading to the malfunction and subsequent death of brain cells. Affected individuals experience deteriorating memory, cognitive abilities, and eventually lose the capability to perform everyday tasks. While no known cure exists for Alzheimer’s, several treatments and interventions aim to alleviate symptoms and decelerate its progression.
A lot of research has been devoted to identifying factors that increase or reduce the risk of developing Alzheimer’s. Studies identified obesity as one such factor, but also pointed that body composition might play a role in this. Lean mass of the body, the difference between total body mass and mass of body fat, tends to be reduced in individuals with Alzheimer’s disease.
Study author Iyas Daghlas and his colleagues wanted to investigate the effect of lean body mass estimated based on genetic factors on the risk of Alzheimer’s disease and on the types of cognitive performance related to the risk of this disease. They hypothesized that higher lean mass would be associated with a reduced risk of Alzheimer’s disease and with better cognitive performance. They conducted a type of research called mendelian research study on the genetic data contained in the UK Biobank.
Study author Iyas Daghlas and his research team aimed to discern the correlation between lean body mass and the risk of Alzheimer’s disease, alongside its influence on cognitive performance markers tied to the disease’s risk. Their hypothesis suggested that an increase in lean mass could correlate with reduced Alzheimer’s risk and enhanced cognitive performance. To verify this, they conducted a type of analysis called Mendelian randomization using genetic data contained in the UK Biobank.
A Mendelian randomization study is a type of genetic research design that uses genetic variations within a group as “natural experiments” to investigate the cause-and-effect relationships between various properties (estimated lean mass in this case) and outcomes (Alzheimer’s disease). By comparing combinations of genetic variants that are randomly inherited at birth and not influenced by external factors, researchers can gain insights into whether a particular property is likely to cause a specific outcome.
For this study, the researchers analyzed data on genetic and body characteristics of 450,243 individuals stored in the UK Biobank. The UK Biobank is a large-scale biomedical database that collects extensive health-related data from large numbers of individuals in the United Kingdom. This data is used for research with the aim to improve the understanding of the links between genetics, lifestyle factors, and diseases. Average age of participants in the analyzed group was 57 years.
The researchers identified specific genetic variants known to be linked with lean body mass variations. Specifically, they concentrated on gene variants differing by a single nucleotide. Using this genetic data, they predicted participants’ lean body mass, factoring out fat mass. (Fat mass is the total mass of tissues used to store energy in the form of fat.) They also estimated lean mass in appendages and the trunk, adjusting for age, gender, and other variables. Similarly, they sought genetic variations tied to Alzheimer’s disease and cognitive performance, but limited their scope to variations correlating with clinically diagnosed late-onset Alzheimer’s disease.
The results indicated that individuals with higher genetically estimated lean mass bore a 12% decreased likelihood of developing Alzheimer’s for every standard deviation increase in lean mass. This correlation held true for total estimated lean mass and lean mass of the trunk. Even after accounting for fat mass and height, the correlation persisted. Intriguingly, body mass index did not show any significant correlation with Alzheimer’s risk.
“In this mendelian randomisation analysis, we found evidence supporting a protective effect of genetically proxied lean mass on the risk of Alzheimer’s disease. Genetically proxied lean mass was associated with increased cognitive performance, but this association did not explain the protective effect of lean mass on the risk of Alzheimer’s disease,” the study authors wrote.
The study makes an important contribution to understanding Alzheimer’s disease risk factors. However, it should be taken into account that the study was based on estimations of lean mass based on genetic data and not on direct measurements. It also remains unknown whether lean mass has a role in Alzheimer’s disease risk only during specific periods of life or throughout the lifetime.
The researchers concluded that their “findings suggest that lean mass might be a possible modifiable protective factor for Alzheimer’s disease. The mechanisms underlying this finding, as well as the clinical and public health implications, warrant further investigation.”
The study, “Genetically proxied lean mass and risk of Alzheimer’s disease: mendelian randomisation study”, was authored by Iyas Daghlas, Malik Nassan, and Dipender Gill.